TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, a...
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doaj-46b57d45beb145bea9ff6802d48d3e052020-11-25T03:24:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00549541883TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell MigrationThibaut Lefebvre0Pierre Rybarczyk1Pierre Rybarczyk2Clara Bretaudeau3Alison Vanlaeys4Rémi Cousin5Sylvie Brassart-Pasco6Denis Chatelain7Isabelle Dhennin-Duthille8Halima Ouadid-Ahidouch9Bertrand Brassart10Mathieu Gautier11Laboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FranceLaboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FranceService d’Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Amiens, FranceUMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), Reims, FranceLaboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FranceUMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), Reims, FranceUMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), Reims, FranceService d’Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Amiens, FranceLaboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FranceLaboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FranceUMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), Reims, FranceLaboratoire de Physiologie Cellulaire et Moléculaire – UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, FrancePancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC.https://www.frontiersin.org/article/10.3389/fcell.2020.00549/fullpancreatic ductal adenocarcinomaelastin-derived peptidestransient receptor potential melastatin-related 7ribosomal protein SAcell migration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thibaut Lefebvre Pierre Rybarczyk Pierre Rybarczyk Clara Bretaudeau Alison Vanlaeys Rémi Cousin Sylvie Brassart-Pasco Denis Chatelain Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Bertrand Brassart Mathieu Gautier |
spellingShingle |
Thibaut Lefebvre Pierre Rybarczyk Pierre Rybarczyk Clara Bretaudeau Alison Vanlaeys Rémi Cousin Sylvie Brassart-Pasco Denis Chatelain Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Bertrand Brassart Mathieu Gautier TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration Frontiers in Cell and Developmental Biology pancreatic ductal adenocarcinoma elastin-derived peptides transient receptor potential melastatin-related 7 ribosomal protein SA cell migration |
author_facet |
Thibaut Lefebvre Pierre Rybarczyk Pierre Rybarczyk Clara Bretaudeau Alison Vanlaeys Rémi Cousin Sylvie Brassart-Pasco Denis Chatelain Isabelle Dhennin-Duthille Halima Ouadid-Ahidouch Bertrand Brassart Mathieu Gautier |
author_sort |
Thibaut Lefebvre |
title |
TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration |
title_short |
TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration |
title_full |
TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration |
title_fullStr |
TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration |
title_full_unstemmed |
TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration |
title_sort |
trpm7/rpsa complex regulates pancreatic cancer cell migration |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2020-07-01 |
description |
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC. |
topic |
pancreatic ductal adenocarcinoma elastin-derived peptides transient receptor potential melastatin-related 7 ribosomal protein SA cell migration |
url |
https://www.frontiersin.org/article/10.3389/fcell.2020.00549/full |
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